metaid_0000024
notes: first order rate constant of appearance/disappearance of tolerance
constant: true
units: metaid_0000041
value: 0.75
name: k_tol
type: Parameter

BIOMD0000000241
parameter: metaid_0000022
units def: metaid_0000041
rule: metaid_0000029
compartment: metaid_0000003
compartment: metaid_0000007
is version of: GO:0008217
species: metaid_0000009
parameter: metaid_0000021
species: metaid_0000011
units def: metaid_1000044
parameter: metaid_0000028
parameter: metaid_0000014
substance units: metaid_0000039
units def: metaid_0000045
rule: metaid_0000030
modified:
  W3 CDTF: Tue Jun 21 13:46:00 BST 2011
parameter: metaid_0000036
event: metaid_0000037
parameter: metaid_0000038
rule: metaid_0000033
units def: metaid_0000040
parameter: metaid_0000035
length unit: length
name: Shi1993_Caffeine_pressor_tolerance
parameter: metaid_0000020
is: MODEL1001080000
rule: metaid_0000034
species: metaid_0000012
parameter: metaid_0000017
type: SBMLModel
occurs in: http://identifiers.org/taxonomy/9606
parameter: metaid_0000019
notes: described in: Pharmacokinetic-pharmacodynamic modeling of caffeine: Tolerance to pressor effects Shi J, Benowitz NL, Denaro CP and Sheiner LB. ; Clin. Pharmacol. Ther. 1993 Jan;53(1):6-14. PMID: 8422743 ; Abstract: We propose a parametric pharmacokinetic-pharmacodynamic model for caffeine that quantifies the development of tolerance to the pressor effect of the drug and characterizes the mean behavior and inter-individual variation of both pharmacokinetics and pressor effect. Our study in a small group of subjects indicates that acute tolerance develops to the pressor effect of caffeine and that both the pressor effect and tolerance occur after some time delay relative to changes in plasma caffeine concentration. The half-life of equilibration of effect with plasma caffeine concentration is about 20 minutes. The half-life of development and regression of tolerance is estimated to be about 1 hour, and the model suggests that tolerance, at its fullest, causes more than a 90 percent reduction of initial (nontolerant) effect. Whereas tolerance to the pressor effect of caffeine develops in habitual coffee drinkers, the pressor response is regained after relatively brief periods of abstinence. Because of the rapid development and regression of tolerance, the pressor response to caffeine depends on how much caffeine is consumed, the schedule of consumption, and the elimination half-life of caffeine. Caffeine intake in this version is modelled as cups of coffee drunk at regular intervals (parameter t_interval ). The amount of caffeine per cup is determined by the parameter cupsize . The body weight of the person drinking is given by the parameter bodyweight . The even coffee cup occures delayed to the drinking of each cup, as the availability of the caffeine in the digestive tract is assumed to be delayed to the ingestion by the time t_lag . This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2011 The BioModels.n…
curated: true
units def: metaid_0000044
parameter: metaid_0000025
parameter: metaid_0000027
parameter: metaid_0100039
parameter: metaid_0000024
rule: metaid_0000031
parameter: metaid_0000026
is version of: GO:0031000
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Lukas
    family: Endler
created:
  W3 CDTF: Fri Jan 08 11:00:59 GMT 2010
units def: metaid_0000039
area units: metaid_0000005
compartment: metaid_0000005
species: metaid_0000013
compartment: metaid_0000004
compartment: metaid_0000008
parameter: metaid_0000016
volume units: metaid_0000003
units def: metaid_0000043
is described by: http://identifiers.org/pubmed/8422743
parameter: metaid_0000018
parameter: metaid_0000015
species: metaid_0000010
time units: metaid_0000040
units def: metaid_0000042
parameter: metaid_0000023
rule: metaid_0000032

metaid_0000020
notes: peripheral to central compartment transport rate
constant: true
units: metaid_0000041
value: 1.19
name: k21
type: Parameter

736595
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

metaid_0000015
notes: apparent volume of the central compartment per kg body-weight
constant: true
units: metaid_0000042
value: 0.32
name: V_C
type: Parameter

metaid_0000005
notes: peripheral compartment
is part of: FMA:20394
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0
name: P
type: Compartment

metaid_0000041
unit: 736534
name: per_hour
type: SBMLUnitsDef

736571
exponent: 1.0
scale: -3
multipler: 1.0
kind: METRE
type: SBMLUnit

metaid_0000019
notes: central to peripheral transport rate
constant: true
units: metaid_0000041
value: 1.64
name: k12
type: Parameter

metaid_0000039
unit: 736510
name: mg
type: SBMLUnitsDef

metaid_0000045
unit: 736644
name: mg_per_kg
type: SBMLUnitsDef

metaid_0000009
initial amount: 0.0
boundary condition: false
name: X_gut
is: SBO:0000241
substance units: metaid_0000045
is: C07481
initial concentration: NaN
constant: false
has only substance units: true
is: CHEBI:27732
type: Species
in compartment: metaid_0000003

metaid_0000010
is: C07481
is: CHEBI:27732
name: C_p
initial concentration: NaN
type: Species
has only substance units: false
in compartment: metaid_0000004
is: SBO:0000247
constant: false
initial amount: 0.0
boundary condition: false

metaid_0000014
notes: overall clearance per kilogram bodyweight
constant: true
value: 0.11
name: CL
type: Parameter

metaid_0000025
notes: base line effect (base MAP)
constant: true
units: metaid_0000043
value: 83.3
name: E_0
type: Parameter

metaid_0000021
constant: true
units: metaid_0000040
value: 3.98
name: t_half
type: Parameter

736644
exponent: 1.0
scale: 0
multipler: 1.0
kind: DIMENSIONLESS
type: SBMLUnit

metaid_0000004
notes: the central compartment, corresponding mainly to the plasma. Its apparant volume is given by the parameterV_C
is version of: FMA:62970
is: SBO:0000290
constant: true
size: 0.31
spatial dimensions: 3.0
name: C
type: Compartment

metaid_0000040
unit: 736522
name: hr
type: SBMLUnitsDef

736619
exponent: 1.0
scale: -6
multipler: 1.0
kind: KILOGRAM
type: SBMLUnit

736510
exponent: 1.0
scale: -6
multipler: 1.0
kind: KILOGRAM
type: SBMLUnit

metaid_0000035
notes: intervall between drinking of cups of coffee
constant: true
units: metaid_0000040
value: 2.0
name: t_intervall
type: Parameter

metaid_0000018
notes: plasma clearance rate
constant: true
units: metaid_0000041
value: 0.34
name: k10
type: Parameter

metaid_0100039
notes: total body weight
constant: true
units: kilogram
value: 80.0
name: bodyweight
type: Parameter

736546
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

metaid_0000038
notes: number of cups drank at time t
constant: false
units: dimensionless
value: 0.0
name: cups
type: Parameter

metaid_0000044
unit: 736607
unit: 736595
unit: 736583
name: mm_Hg per (mg/l)
type: SBMLUnitsDef

metaid_0000028
notes: effect (mean arterial pressure, MAP)
constant: false
units: metaid_0000043
value: NaN
name: MAP
type: Parameter

metaid_0000011
boundary condition: false
type: Species
name: C_per
has only substance units: false
is: SBO:0000247
constant: false
is: C07481
in compartment: metaid_0000005
initial concentration: 0.0
initial amount: NaN
is: CHEBI:27732

metaid_0000008
notes: virtual effect compartment
is: SBO:0000289
constant: true
size: 1.0
spatial dimensions: 3.0
name: Eff
type: Compartment

metaid_0000017
notes: time lag between drinking of coffee and arrival in gastrointestinal tract
constant: true
units: metaid_0000040
value: 0.15
name: t_lag
type: Parameter

metaid_0000022
notes: bioavailability
constant: true
value: 0.984
name: F
type: Parameter

736559
exponent: -1.0
scale: 0
multipler: 1.0
kind: KILOGRAM
type: SBMLUnit

metaid_0000003
notes: gut compartment, the digestive tract
is version of: FMA:71132
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0
name: Gut
type: Compartment

metaid_0000036
notes: amount of caffeine per cup
constant: true
units: metaid_0000039
value: 90.0
name: cupsize
type: Parameter

736607
exponent: -1.0
scale: -6
multipler: 1.0
kind: KILOGRAM
type: SBMLUnit

metaid_0000012
is version of: CHEBI:27732
type: Species
constant: false
notes: hypothetical effect-site concentration
initial concentration: 0.0
has only substance units: false
name: C_e
initial amount: NaN
boundary condition: false
is: SBO:0000241
in compartment: metaid_0000008

736583
exponent: 1.0
scale: -3
multipler: 1.0
kind: METRE
type: SBMLUnit

736522
exponent: 1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

metaid_0000007
notes: virtual compartment to account for tolerance effects
is: SBO:0000289
constant: true
size: 1.0
spatial dimensions: 3.0
name: Tol
type: Compartment

metaid_0000027
constant: true
units: metaid_1000044
value: 0.26
name: T_50
type: Parameter

metaid_0000043
unit: 736571
notes: unit for blood pressure
name: mm_Hg
type: SBMLUnitsDef

metaid_0000016
constant: true
units: metaid_0000041
value: 12.0
name: k_a
type: Parameter

736656
persistant: true
initial value: true
type: Trigger

metaid_0000023
notes: first order rate of entry/exit to/from effector site
constant: true
units: metaid_0000041
value: 2.03
name: k_eo
type: Parameter

metaid_0000037
event assignment: 736680
event assignment: 736668
trigger: 736656
notes: availability of caffeine in gut after drinking a cup
use values from trigger time: true
name: coffee cup
type: Event

metaid_0000042
unit: 736559
unit: 736546
name: liter_per_kg
type: SBMLUnitsDef

736632
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

metaid_1000044
unit: 736632
unit: 736619
name: mg/l
type: SBMLUnitsDef

metaid_0000013
type: Species
constant: false
boundary condition: false
notes: hypothetical antagonistic metabolite to account for tolerance development
name: C_t
has only substance units: false
initial amount: NaN
in compartment: metaid_0000007
is: SBO:0000241
initial concentration: 0.0
is version of: CHEBI:27732

metaid_0000026
constant: true
units: metaid_0000044
value: 19.07
name: S
type: Parameter

736534
exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit